Integrated Omics and Multicohort Analyses Identify an Enhancer Variant Linking Ferroptosis to Precision Therapy in Prostate Cancer.

ABSTRACT: Prostate cancer is the most prevalent cancer among men worldwide and exhibits significant genetic heritability. In this study, we performed an integrative analysis combining chromatin accessibility profiling, transcriptomics, and two-stage case-control studies, alongside an unbiased phenome-wide exploration in the FinnGen cohort. This comprehensive approach identified the enhancer-associated SNP rs7077830 at chromosome 10q11 as a critical modulator of prostate cancer susceptibility. Mechanistic investigations revealed that rs7077830 exerted allele-specific enhancer activity, driving NCOA4 expression via a ZNF384-mediated enhancer-promoter interaction. CRISPR/Cas9-mediated single-nucleotide editing confirmed the direct regulatory role of rs7077830 on NCOA4 and its contribution to prostate c

SUBMITTER: Ma S 

PROVIDER: S-EPMC12485374 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature